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Opiate Receptors and Antagonists pp 99–118Cite as

Medicinal Chemistry of Kappa Opioid Receptor Antagonists

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Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

The kappa opioid receptor (KOR), a member of the opioid receptor family, was initially studied for its involvement in the mediation of pain. More recently, there has been growing interest in selective KOR agents for their potential effects on mood and reward. In particular, selective KOR antagonists may offer a novel approach to relieve symptoms of depression. In this chapter, we describe the structure–activity relationships (SAR) of nonpeptidic KOR antagonists. Specifically, we review the SAR of norbinaltorphimine (norBNI) and its structur ally simplified derivative GNTI. We present the SAR of JDTic and the recently developed MTHQ. The SAR patterns of norBNI have been extensively studied, but there have been relatively fewer studies on the SAR of JDTic and MTHQ. While the overall SAR trends of these structurally distinct agents differ, there appears to be a common requirement for KOR inhibition: the presence of a phenol unit and a basic nitrogen. In the second part of this chapter, we discuss the unusually long duration of action of the available KOR antagonists and make suggestions on pos sibilities for the design of additional KOR antagonists.

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Authors and Affiliations

  1. Molecular Pharmacology Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA, 02478

    Cécile Béguin & Bruce M. Cohen

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  1. Cécile Béguin
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  2. Bruce M. Cohen
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Editors and Affiliations

  1. Life Sciences/Toxicology, Alkermes, Inc., Cambridge, MA, 02139, USA

    Reginald L. Dean III

  2. Department of Pharmacology, College of Osteopathic Medicine, University of New England, Biddleford, ME, 04005, USA

    Edward J. Bilsky

  3. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA

    S. Stevens Negus

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Béguin, C., Cohen, B.M. (2009). Medicinal Chemistry of Kappa Opioid Receptor Antagonists. In: Dean, R.L., Bilsky, E.J., Negus, S.S. (eds) Opiate Receptors and Antagonists. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-59745-197-0_6

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